Methodology gaps in Medicine

Representative open questions

Showing 30 of 584 — one per source paper, highest-quality first.

• CUIDADO TRANSICIONAL HOSPITAL-DOMICÍLIO REALIZADO POR ENFERMEIRAS A PESSOAS IDOSAS COM MARCAPASSO ARTIFICIAL: PROTOCOLO DE REVISÃO DE ESCOPO (2026) · doi

  The scoping review protocol does not specify a critical quality assessment methodology for evaluating the methodological quality of included studies on transitional hospital-to-home nursing care for elderly patients with artificial pacemakers. While the authors mention that quality evaluation will not be performed per JBI guidelines for scoping reviews, potential methodological limitations in the primary studies will only be described in the synthesis without formal assessment tools.

• The impact of traumatic injury on the respiratory system; a narrative review of injury-associated and clinically-induced mechanisms of trauma-associated pneumonia (2026) · doi

  Supine body positioning has been identified as a risk factor for ventilator-associated pneumonia in mechanically ventilated patients, but the specific effects of patient positioning on microaspiration and bacterial colonization in trauma patients with multiple rib fractures and altered chest wall mechanics have not been rigorously studied.

• FDG-PET/CT based small volume accelerated immuno chemoradiotherapy in locally advanced NSCLC (PACCELIO) – a randomized, open-label, multicenter phase II trial protocol (2026) · doi

  The trial prospectively evaluates immunomarkers (NLR, ALI) and immune-related radiotherapy planning parameters (EDIC, PET-related imaging parameters) in NSCLC, but the specific mechanistic relationships between these biomarkers and response to hypofractionated, accelerated chemoradiotherapy combined with consolidative immunotherapy have not been established. The longitudinal kinetics of these immunomarkers during the condensed treatment schedule require quantitative correlation analysis with clinical outcomes.

• Impact of Health Education and Preventive Interventions on Non- Communicable Diseases in Rural Communities: A Community-Based Randomized Controlled Trial (2026) · doi

  The intervention group achieved significant systolic blood pressure reduction (14.45 mmHg) and BMI reduction, but the paper does not disaggregate which components of the structured lifestyle counseling—dietary education, physical activity promotion, or medication adherence counseling—drove these improvements in obesity-related hypertension treatment.

• Neurosurgery as an immune anchor point: a translational framework for perioperative immunoengineering (2026) · doi

  The paper references tissue biorepository infrastructure for clinical translation but does not specify standardized protocols for longitudinal immune profiling of perioperative neuroimmune changes in neurosurgical patients. Comparative characterization of macrophage subsets at the meningeal margin across different surgical procedures and timepoints post-resection is needed to establish mechanistic benchmarks.

• The neuro-immune axis in preeclampsia: from the maternal-fetal interface to systemic dysregulation (2026) · doi

  The paper proposes that targeted modulation of central autonomic or sensory integration circuits may reduce neurological manifestations such as eclampsia or cerebral autoregulation failure in preclinical models, but does not specify which circuit targets (e.g., nucleus tractus solitarius, dorsal motor nucleus, insular cortex) should be prioritized or what modulation techniques (optogenetics, chemogenetics, pharmacological interventions) should be tested.

• The use of artificial intelligence based modelling techniques in One Health-related infectious disease studies in Sub-Saharan Africa: a review (2026) · doi

  The review protocol was not prospectively registered in a public registry such as PROSPERO prior to conducting the systematic literature search, limiting the transparency and reproducibility of the review methodology.

• What is The Effect of Early Enteral Nutrition on Mortality in Critically Ill Patients Receiving Vasopressor Support? : A Systematic Review (2026) · doi

  Multiple studies identified varying vasopressor dose thresholds for safe enteral nutrition initiation (≤0.14 µg/kg/min by Merchan et al., <0.3 µg/kg/min by Luping Wang et al., 0.23 µg/kg/min by Fan Qi et al.), but no prospective study has prospectively validated which norepinephrine-equivalent dose cutoff, in combination with clinical perfusion parameters, reliably predicts enteral feeding tolerance and prevents mesenteric ischemia across different patient populations.

• Decision-ready evidence for vital pulp therapy: a network meta-analysis of bioactive materials in mature permanent teeth (2026) · doi

  Diagnostic thresholds for symptomatic teeth in vital pulp therapy studies were heterogeneous, introducing classification noise that could not be fully eliminated even with composite outcome definitions and sensitivity analyses. Standardized diagnostic criteria and symptom severity scales (e.g., Visual Analogue Scale pain scoring, percussion response grading) should be adopted prospectively in RCTs comparing pulpotomy outcomes in symptomatic mature permanent teeth.

• Exercise benefits in metabolism on cardiovascular disease (2026) · doi

  High-throughput proteomics have uncovered exercise training and type 2 diabetes-induced changes in human white adipose tissue, but comparative proteomic analysis across different exercise modalities, duration, and intensity levels in cardiovascular disease populations has not been systematically characterized to identify tissue-specific biomarkers.

• Management of depression utilizing Traditional Chinese Medicine (2026) · doi

  Non-pharmacological TCM modalities such as acupuncture and herbal baths are clinically promising for depression symptom relief but demand deeper mechanistic scrutiny, including reproducibility of neurochemical changes and determination of pharmacokinetic profiles of active agents in these delivery systems.

• A systematic review of sample size determination in Bayesian randomized clinical trials: full Bayesian methods are rarely used (2026) · doi

  The adaptive platform trial designs documented (HEALEY ALS Platform Trial, REMAP-CAP, PRINCIPLE trials) use hybrid or unspecified sample size methods, but there is insufficient evidence on optimal Bayesian sample size determination strategies specifically designed for multi-arm, multi-stage adaptive platform trial architectures with shared control arms.

• Unveiling the relationship of the comorbidity between depression and type 2 diabetes mellitus: a macro analysis and micro interpretation (2026) · doi

  Bibliometric tools currently lack the capability to differentiate between author names with identical abbreviations in depression and T2DM comorbidity studies. Developing disambiguation algorithms specifically trained on medical literature author datasets would improve accuracy of author contribution tracking and citation analysis in this research domain.

• A behaviour and disease model of testing and isolation (2026) · doi

  The model does not incorporate severe case outcomes (hospitalisations and deaths) despite population perception of illness threat potentially varying by case severity over an outbreak. Refinement is needed to include hospitalisation and death dynamics, with parameterisation of how the population's behavioural response shifts when attributed different importance to cases versus hospitalisations versus deaths.

• Artificial intelligence in acute and critical care: current challenges and strategic solutions (2026) · doi

  Fine-tuning combined with retrieval-augmented generation for error-detection and self-correction capabilities in AI systems for acute and critical care requires systematic evaluation and validation. The paper identifies this as a needed approach but does not specify implementation protocols, benchmark datasets, or performance metrics for testing these combined techniques in complex clinical scenarios.

• Peran Tenaga Kesehatan dalam Penanganan Penyakit Degeneratif pada Lansia di Puskesmas Negeri Lama: Sebuah Studi Kasus (2026) · doi

  Mixed-methods research combining in-depth interviews with elderly patients and families alongside quantitative measurement of quality of life using WHOQOL-BREF or EQ-5D questionnaires and clinical outcomes (blood pressure, blood glucose) has not been conducted to capture both patient perspectives and objective health metrics in degenerative disease management at primary health centers.

• Artificial intelligence approaches to predicting treatment non-adherence in chronic diseases: a narrative review (2026) · doi

  The literature demonstrates considerable heterogeneity in disease contexts, data sources, model architectures, and adherence outcome definitions across chronic disease adherence prediction studies, which constrains direct comparison of machine learning model performance. Standardized frameworks for defining adherence outcomes and model evaluation metrics across diverse chronic conditions are needed to enable systematic benchmarking.

• Evidence-based approaches for Empty Nose Syndrome management: a systematic review highlighting current treatments and future directions (2026) · doi

  Objective evaluation metrics for Empty Nose Syndrome treatment outcomes require development and validation to be consistently applied across different studies; solutions such as using natural disease progression as a control and independent assessor blinding need implementation but lack specific operational definitions.

• Multimodal artificial intelligence in urologic precision oncology: from algorithm to translational medicine (a systemized narrative review) (2026) · doi

  Multimodal AI systems for prostate cancer diagnosis require clinician participation in development (reference 48), yet the specific frameworks, validation protocols, and training methodologies for ensuring effective human-AI collaboration between urologists, pathologists, and radiologists have not been comprehensively defined.

• Biochemical Markers In Seminal Plasma And Serum: A Comparative Assessment In Fertile And Infertile Men (2026) · doi

  Standardized protocols for biomarker evaluation in seminal plasma and serum—including sample collection, processing, and analysis procedures—are necessary to convert research findings on male fertility markers (SGOT, LDH, cholesterol, copper, glucose) into clinical practice and enable integration into standard clinical procedures.

• Echocardiographic Assessment of Left Ventricular Mass Regression and Functional Changes after Bariatric Surgery (2026) · doi

  The authors report that LV mass index was not calculated in their analysis of cardiac remodeling after bariatric surgery. Inclusion of indexed LV mass measurements (normalized to body surface area) is needed to better quantify left ventricular mass regression independent of body size changes.

• Principles and ethics in medicine (2020) · doi

  The paper discusses virtue ethics as aligning with traditional professional conduct models like the Hippocratic Oath and General Medical Council's Good Medical Practice guidelines, but does not specify empirical methods to assess whether virtuous character development in medical training actually produces better clinical outcomes or improved patient satisfaction compared to principle-based or consequentialist training approaches.

• The portability paradox of foundation models for clinical decision support (2026) · doi

  Foundation models show improved performance with scale (reference 32), but the minimum dataset size and clinical outcome diversity required for effective few-shot fine-tuning of foundation models on rare diseases (reference 29) and domain-specific conditions like cervical spondylotic myelopathy (reference 24) has not been systematically determined across different clinical populations.

• Reflections on Medicine in Japan (2015) · doi

  The paper notes opportunities for early, sensitive conversations with patients and families about illness nature, disease natural history, and treatment benefits/risks in the context of Advanced Health Care Directives, but provides no standardized communication framework or validated assessment tools for measuring quality or outcomes of these discussions.

• Antipsychotics (2020) · doi

  The paper recommends starting with low doses and increasing cautiously in elderly patients and those with renal impairment, but does not provide specific dose escalation schedules, clearance adjustment formulas, or validated dosing algorithms tailored to these vulnerable populations for antipsychotics.

• Evidence-based Medicine: Alternative Medicine [Non-drug Medicine, CAM] versus Pharmacological Medicine (2015) · doi

  The paper identifies four fundamental problems with randomized clinical trials (RCTs) used to document chemical medicine efficacy, but does not specify what alternative evidence-based study designs should be employed to validate non-drug medicine and CAM interventions with comparable methodological rigor.

• Evasive Eragrostis: A Unique Case of Intralingual Plant Implantation with Persistent Viability (2026) · doi

  The diagnostic imaging protocol for plant foreign body retention lacks standardized interpretation criteria to differentiate plant material from fluid accumulation and soft tissue appearance; the paper notes potential overlap but does not provide specific radiological features or a validated scoring system for distinguishing plant-induced inflammatory lesions from other intralingual masses.

• Impact of Adjuvant Oral Care on Clinical Outcomes in Mechanically Ventilated ICU Patients: A Randomized Controlled Trial (2026) · doi

  The paper does not specify the exact composition, frequency, or duration of the structured oral care protocol used in the intervention group. Future studies should standardize and clearly define the oral care regimen parameters (e.g., specific antimicrobial agents, brushing frequency, duration of each intervention) to enable reproducibility and comparison across different ICU settings.

• Emergencies in palliative medicine (2011) · doi

  Confusion occurs in up to 85% of advanced cancer patients with multiple documented causes (dehydration, infection, hypercalcaemia, uraemia, hyponatraemia, hypoxia, drugs), but the paper does not provide a decision algorithm or evidence-based protocol for systematically distinguishing which etiologies to prioritize in sequential treatment or how to predict treatment responsiveness.

• Allocation of resources in medicine – a moral imperative for doctors as well (2020) · doi

  The paper discusses the importance of improved communication and discernment on the micro-level to shift patient autonomy understanding, but does not specify which communication techniques, decision-aid tools, or shared decision-making frameworks have been empirically validated for explaining test necessity and harm without mentioning resource allocation.